diff --git a/src/arduino/Adafruit_USBH_Host.cpp b/src/arduino/Adafruit_USBH_Host.cpp
index cdba7732..c7254609 100644
--- a/src/arduino/Adafruit_USBH_Host.cpp
+++ b/src/arduino/Adafruit_USBH_Host.cpp
@@ -211,11 +211,14 @@ void tuh_max3421_spi_cs_api(uint8_t rhport, bool active) {
   SPIClass *spi = host->_spi;
 
   if (active) {
-    // MAX3421e max clock is 26MHz
-    // Depending on mcu ports, it may need to be clipped down
+    // MAX3421e max clock is 26MHz. SAMD SERCOM clocks are quantized by the
+    // baud generator, so request values that stay within each port's limit.
 #ifdef ARDUINO_ARCH_SAMD
-    // SAMD 21/51 can only work reliably at 12MHz
+#if TU_CHECK_MCU(OPT_MCU_SAMD51, OPT_MCU_SAME5X)
+    uint32_t const max_clock = 25000000ul;
+#else
     uint32_t const max_clock = 12000000ul;
+#endif
 #else
     uint32_t const max_clock = 26000000ul;
 #endif
@@ -273,11 +276,20 @@ void tuh_max3421_int_api(uint8_t rhport, bool enabled) {
   (void)host;
 
 #ifdef ARDUINO_ARCH_SAMD
-  //--- SAMD51 ---//
-#ifdef __SAMD51__
+//--- SAMD51/SAME51 ---//
+#if TU_CHECK_MCU(OPT_MCU_SAMD51)
   const IRQn_Type irq =
       (IRQn_Type)(EIC_0_IRQn + g_APinDescription[host->_intr].ulExtInt);
 
+  if (enabled) {
+    NVIC_EnableIRQ(irq);
+  } else {
+    NVIC_DisableIRQ(irq);
+  }
+#elif TU_CHECK_MCU(OPT_MCU_SAME5X)
+  const IRQn_Type irq =
+      (IRQn_Type)(EIC_EXTINT_0_IRQn + g_APinDescription[host->_intr].ulExtInt);
+
   if (enabled) {
     NVIC_EnableIRQ(irq);
   } else {
diff --git a/src/arduino/ports/samd/Adafruit_TinyUSB_samd.cpp b/src/arduino/ports/samd/Adafruit_TinyUSB_samd.cpp
index f6fe45e0..214d3fe6 100644
--- a/src/arduino/ports/samd/Adafruit_TinyUSB_samd.cpp
+++ b/src/arduino/ports/samd/Adafruit_TinyUSB_samd.cpp
@@ -37,7 +37,7 @@
 //--------------------------------------------------------------------+
 extern "C" {
 
-#if CFG_TUSB_MCU == OPT_MCU_SAMD51 || CFG_TUSB_MCU == OPT_MCU_SAME5X
+#if TU_CHECK_MCU(OPT_MCU_SAMD51)
 
 // SAMD51
 void USB_0_Handler(void) { tud_int_handler(0); }
@@ -45,7 +45,15 @@ void USB_1_Handler(void) { tud_int_handler(0); }
 void USB_2_Handler(void) { tud_int_handler(0); }
 void USB_3_Handler(void) { tud_int_handler(0); }
 
-#elif CFG_TUSB_MCU == OPT_MCU_SAMD21
+#elif TU_CHECK_MCU(OPT_MCU_SAME5X)
+
+// SAME53/54
+void USB_OTHER_Handler(void) { tud_int_handler(0); }
+void USB_SOF_HSOF_Handler(void) { tud_int_handler(0); }
+void USB_TRCPT0_Handler(void) { tud_int_handler(0); }
+void USB_TRCPT1_Handler(void) { tud_int_handler(0); }
+
+#elif TU_CHECK_MCU(OPT_MCU_SAMD21)
 
 // SAMD21
 void USB_Handler(void) { tud_int_handler(0); }
@@ -61,7 +69,7 @@ void TinyUSB_Port_InitDevice(uint8_t rhport) {
   (void)rhport;
 
   /* Enable USB clock */
-#if defined(__SAMD51__)
+#if TU_CHECK_MCU(OPT_MCU_SAMD51)
   MCLK->APBBMASK.reg |= MCLK_APBBMASK_USB;
   MCLK->AHBMASK.reg |= MCLK_AHBMASK_USB;
 
@@ -84,6 +92,29 @@ void TinyUSB_Port_InitDevice(uint8_t rhport) {
   NVIC_SetPriority(USB_1_IRQn, 0UL);
   NVIC_SetPriority(USB_2_IRQn, 0UL);
   NVIC_SetPriority(USB_3_IRQn, 0UL);
+#elif TU_CHECK_MCU(OPT_MCU_SAME5X)
+  MCLK->APBBMASK.reg |= MCLK_APBBMASK_USB;
+  MCLK->AHBMASK.reg |= MCLK_AHBMASK_USB;
+
+  // Set up the USB DP/DN pins
+  PORT->Group[0].PINCFG[PIN_PA24H_USB_DM].bit.PMUXEN = 1;
+  PORT->Group[0].PMUX[PIN_PA24H_USB_DM / 2].reg &=
+      ~(0xF << (4 * (PIN_PA24H_USB_DM & 0x01u)));
+  PORT->Group[0].PMUX[PIN_PA24H_USB_DM / 2].reg |=
+      MUX_PA24H_USB_DM << (4 * (PIN_PA24H_USB_DM & 0x01u));
+  PORT->Group[0].PINCFG[PIN_PA25H_USB_DP].bit.PMUXEN = 1;
+  PORT->Group[0].PMUX[PIN_PA25H_USB_DP / 2].reg &=
+      ~(0xF << (4 * (PIN_PA25H_USB_DP & 0x01u)));
+  PORT->Group[0].PMUX[PIN_PA25H_USB_DP / 2].reg |=
+      MUX_PA25H_USB_DP << (4 * (PIN_PA25H_USB_DP & 0x01u));
+
+  GCLK->PCHCTRL[USB_GCLK_ID].reg =
+      GCLK_PCHCTRL_GEN_GCLK1_Val | (1 << GCLK_PCHCTRL_CHEN_Pos);
+
+  NVIC_SetPriority(USB_OTHER_IRQn, 0UL);
+  NVIC_SetPriority(USB_SOF_HSOF_IRQn, 0UL);
+  NVIC_SetPriority(USB_TRCPT0_IRQn, 0UL);
+  NVIC_SetPriority(USB_TRCPT1_IRQn, 0UL);
 #else
   PM->APBBMASK.reg |= PM_APBBMASK_USB;
 
@@ -126,7 +157,7 @@ void TinyUSB_Port_EnterDFU(void) {
 }
 
 uint8_t TinyUSB_Port_GetSerialNumber(uint8_t serial_id[16]) {
-#ifdef __SAMD51__
+#if TU_CHECK_MCU(OPT_MCU_SAMD51, OPT_MCU_SAME5X)
   uint32_t *id_addresses[4] = {(uint32_t *)0x008061FC, (uint32_t *)0x00806010,
                                (uint32_t *)0x00806014, (uint32_t *)0x00806018};
 #else // samd21
diff --git a/src/arduino/ports/samd/tusb_config_samd.h b/src/arduino/ports/samd/tusb_config_samd.h
index d2276d12..f4875022 100644
--- a/src/arduino/ports/samd/tusb_config_samd.h
+++ b/src/arduino/ports/samd/tusb_config_samd.h
@@ -32,8 +32,10 @@ extern "C" {
 //--------------------------------------------------------------------
 // COMMON CONFIGURATION
 //--------------------------------------------------------------------
-#ifdef __SAMD51__
+#if defined(__SAMD51__) || defined(__SAME51__)
 #define CFG_TUSB_MCU OPT_MCU_SAMD51
+#elif defined(__SAME53__) || defined(__SAME54__)
+#define CFG_TUSB_MCU OPT_MCU_SAME5X
 #else
 #define CFG_TUSB_MCU OPT_MCU_SAMD21
 #endif
diff --git a/src/portable/microchip/samd/dcd_samd.c b/src/portable/microchip/samd/dcd_samd.c
index cdfb00e3..c21e94ea 100644
--- a/src/portable/microchip/samd/dcd_samd.c
+++ b/src/portable/microchip/samd/dcd_samd.c
@@ -29,6 +29,7 @@
 #if CFG_TUD_ENABLED && TU_CHECK_MCU(OPT_MCU_SAMD11, OPT_MCU_SAMD21, OPT_MCU_SAML2X, OPT_MCU_SAMD51, OPT_MCU_SAME5X)
 
 #include "sam.h"
+#include "same5x_usb.h"
 #include "device/dcd.h"
 
 /*------------------------------------------------------------------*/
@@ -103,7 +104,7 @@ bool dcd_init(uint8_t rhport, const tusb_rhport_init_t* rh_init) {
   return true;
 }
 
-#if TU_CHECK_MCU(OPT_MCU_SAMD51, OPT_MCU_SAME5X)
+#if TU_CHECK_MCU(OPT_MCU_SAMD51)
 void dcd_int_enable(uint8_t rhport) {
   (void) rhport;
   NVIC_EnableIRQ(USB_0_IRQn);
@@ -120,6 +121,23 @@ void dcd_int_disable(uint8_t rhport) {
   NVIC_DisableIRQ(USB_0_IRQn);
 }
 
+#elif TU_CHECK_MCU(OPT_MCU_SAME5X)
+void dcd_int_enable(uint8_t rhport) {
+  (void) rhport;
+  NVIC_EnableIRQ(USB_OTHER_IRQn);
+  NVIC_EnableIRQ(USB_SOF_HSOF_IRQn);
+  NVIC_EnableIRQ(USB_TRCPT0_IRQn);
+  NVIC_EnableIRQ(USB_TRCPT1_IRQn);
+}
+
+void dcd_int_disable(uint8_t rhport) {
+  (void) rhport;
+  NVIC_DisableIRQ(USB_TRCPT1_IRQn);
+  NVIC_DisableIRQ(USB_TRCPT0_IRQn);
+  NVIC_DisableIRQ(USB_SOF_HSOF_IRQn);
+  NVIC_DisableIRQ(USB_OTHER_IRQn);
+}
+
 #elif TU_CHECK_MCU(OPT_MCU_SAMD11, OPT_MCU_SAMD21, OPT_MCU_SAML2X)
 void dcd_int_enable(uint8_t rhport) {
   (void) rhport;
diff --git a/src/portable/microchip/samd/hcd_samd.c b/src/portable/microchip/samd/hcd_samd.c
index 0de7ddeb..110190af 100644
--- a/src/portable/microchip/samd/hcd_samd.c
+++ b/src/portable/microchip/samd/hcd_samd.c
@@ -31,6 +31,7 @@
 
 #include "host/hcd.h"
 #include "sam.h"
+#include "same5x_usb.h"
 
 /*------------------------------------------------------------------*/
 /* MACRO TYPEDEF CONSTANT ENUM
@@ -425,7 +426,7 @@ bool hcd_init(uint8_t rhport, const tusb_rhport_init_t* rh_init) {
   return true;
 }
 
-#if TU_CHECK_MCU(OPT_MCU_SAMD51, OPT_MCU_SAME5X)
+#if TU_CHECK_MCU(OPT_MCU_SAMD51)
 
 // Enable USB interrupt
 void hcd_int_enable(uint8_t rhport)
@@ -447,6 +448,28 @@ void hcd_int_disable(uint8_t rhport)
   NVIC_DisableIRQ(USB_0_IRQn);
 }
 
+#elif TU_CHECK_MCU(OPT_MCU_SAME5X)
+
+// Enable USB interrupt
+void hcd_int_enable(uint8_t rhport)
+{
+  (void) rhport;
+  NVIC_EnableIRQ(USB_OTHER_IRQn);
+  NVIC_EnableIRQ(USB_SOF_HSOF_IRQn);
+  NVIC_EnableIRQ(USB_TRCPT0_IRQn);
+  NVIC_EnableIRQ(USB_TRCPT1_IRQn);
+}
+
+// Disable USB interrupt
+void hcd_int_disable(uint8_t rhport)
+{
+  (void) rhport;
+  NVIC_DisableIRQ(USB_TRCPT1_IRQn);
+  NVIC_DisableIRQ(USB_TRCPT0_IRQn);
+  NVIC_DisableIRQ(USB_SOF_HSOF_IRQn);
+  NVIC_DisableIRQ(USB_OTHER_IRQn);
+}
+
 #elif TU_CHECK_MCU(OPT_MCU_SAMD11, OPT_MCU_SAMD21, OPT_MCU_SAML2X)
 
 // Enable USB interrupt
diff --git a/src/portable/microchip/samd/same5x_usb.h b/src/portable/microchip/samd/same5x_usb.h
new file mode 100644
index 00000000..3dc9fbce
--- /dev/null
+++ b/src/portable/microchip/samd/same5x_usb.h
@@ -0,0 +1,85 @@
+/*
+ * The MIT License (MIT)
+ *
+ * Copyright (c) 2026 Chris Rabel
+ *
+ * Permission is hereby granted, free of charge, to any person obtaining a copy
+ * of this software and associated documentation files (the "Software"), to deal
+ * in the Software without restriction, including without limitation the rights
+ * to use, copy, modify, merge, publish, distribute, sublicense, and/or sell
+ * copies of the Software, and to permit persons to whom the Software is
+ * furnished to do so, subject to the following conditions:
+ *
+ * The above copyright notice and this permission notice shall be included in
+ * all copies or substantial portions of the Software.
+ *
+ * THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR
+ * IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY,
+ * FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL THE
+ * AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER
+ * LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM,
+ * OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN
+ * THE SOFTWARE.
+ */
+
+#ifndef _SAME5X_USB_H_
+#define _SAME5X_USB_H_
+
+#if defined(__GNUC__)
+#pragma GCC system_header
+#endif
+
+#include "tusb_option.h"
+
+#if TU_CHECK_MCU(OPT_MCU_SAME5X)
+
+#ifndef _Ul
+#define _Ul(x) x##U
+#endif
+
+#ifndef TUSB_SAME5X_COMPAT_ROREG8
+#define TUSB_SAME5X_COMPAT_ROREG8 1
+typedef volatile const uint8_t RoReg8;
+#endif
+
+#if defined(__has_include)
+#if __has_include("samd51/include/component/usb.h")
+#include "samd51/include/component/usb.h"
+#else
+#error "SAME5x USB support requires SAMD51 USB component headers on the include path."
+#endif
+#else
+#include "samd51/include/component/usb.h"
+#endif
+
+#if !defined(NVMCTRL_SW0) && defined(SW0_ADDR)
+#define NVMCTRL_SW0 SW0_ADDR
+#elif !defined(NVMCTRL_SW0) && defined(SW0_FUSES_BASE_ADDRESS)
+#define NVMCTRL_SW0 SW0_FUSES_BASE_ADDRESS
+#endif
+
+#ifndef USB_FUSES_TRANSN_ADDR
+#define USB_FUSES_TRANSN_ADDR (NVMCTRL_SW0 + 4)
+#define USB_FUSES_TRANSN_Pos 0
+#define USB_FUSES_TRANSN_Msk (_Ul(0x1F) << USB_FUSES_TRANSN_Pos)
+#endif
+
+#ifndef USB_FUSES_TRANSP_ADDR
+#define USB_FUSES_TRANSP_ADDR (NVMCTRL_SW0 + 4)
+#define USB_FUSES_TRANSP_Pos 5
+#define USB_FUSES_TRANSP_Msk (_Ul(0x1F) << USB_FUSES_TRANSP_Pos)
+#endif
+
+#ifndef USB_FUSES_TRIM_ADDR
+#define USB_FUSES_TRIM_ADDR (NVMCTRL_SW0 + 4)
+#define USB_FUSES_TRIM_Pos 10
+#define USB_FUSES_TRIM_Msk (_Ul(0x7) << USB_FUSES_TRIM_Pos)
+#endif
+
+#if !defined(USB) && defined(USB_REGS)
+#define USB ((Usb *)USB_REGS)
+#endif
+
+#endif
+
+#endif