diff --git a/Marlin/MarlinConfig.h b/Marlin/MarlinConfig.h
index 245974eb7..5f77dba0e 100644
--- a/Marlin/MarlinConfig.h
+++ b/Marlin/MarlinConfig.h
@@ -31,7 +31,7 @@
 #include "Conditionals_LCD.h"
 #include "Configuration_adv.h"
 #include "pins.h"
-#ifndef USBCON
+#if defined(__AVR__) && !defined(USBCON)
   #define HardwareSerial_h // trick to disable the standard HWserial
 #endif
 #include "Arduino.h"
diff --git a/Marlin/MarlinSerial.cpp b/Marlin/MarlinSerial.cpp
index dfea17cff..1b288b67b 100644
--- a/Marlin/MarlinSerial.cpp
+++ b/Marlin/MarlinSerial.cpp
@@ -34,7 +34,7 @@
 
 #include "MarlinConfig.h"
 
-#if !defined(USBCON) && (defined(UBRRH) || defined(UBRR0H) || defined(UBRR1H) || defined(UBRR2H) || defined(UBRR3H))
+#if !(defined(__AVR__) && defined(USBCON)) && (defined(UBRRH) || defined(UBRR0H) || defined(UBRR1H) || defined(UBRR2H) || defined(UBRR3H))
 
   #include "MarlinSerial.h"
   #include "Marlin.h"
@@ -651,9 +651,9 @@
   // Preinstantiate
   MarlinSerial customizedSerial;
 
-#endif // !USBCON && (UBRRH || UBRR0H || UBRR1H || UBRR2H || UBRR3H)
+#endif // !(__AVR__ && USBCON) && (UBRRH || UBRR0H || UBRR1H || UBRR2H || UBRR3H)
 
 // For AT90USB targets use the UART for BT interfacing
-#if defined(USBCON) && ENABLED(BLUETOOTH)
+#if defined(__AVR__) && defined(USBCON) && ENABLED(BLUETOOTH)
   HardwareSerial bluetoothSerial;
 #endif
diff --git a/Marlin/MarlinSerial.h b/Marlin/MarlinSerial.h
index 8603b654f..0cd15a599 100644
--- a/Marlin/MarlinSerial.h
+++ b/Marlin/MarlinSerial.h
@@ -85,7 +85,7 @@
   #define TX_BUFFER_SIZE 32
 #endif
 
-#ifndef USBCON
+#if !(defined(__AVR__) && defined(USBCON))
 
   #if RX_BUFFER_SIZE > 256
     typedef uint16_t ring_buffer_pos_t;
@@ -163,10 +163,10 @@
 
   extern MarlinSerial customizedSerial;
 
-#endif // !USBCON
+#endif // !(__AVR__ && USBCON)
 
 // Use the UART for Bluetooth in AT90USB configurations
-#if defined(USBCON) && ENABLED(BLUETOOTH)
+#if defined(__AVR__) && defined(USBCON) && ENABLED(BLUETOOTH)
   extern HardwareSerial bluetoothSerial;
 #endif
 
diff --git a/Marlin/Marlin_main.cpp b/Marlin/Marlin_main.cpp
index db4c5f0fe..b3e0ff449 100644
--- a/Marlin/Marlin_main.cpp
+++ b/Marlin/Marlin_main.cpp
@@ -13848,7 +13848,7 @@ void loop() {
           card.closefile();
           SERIAL_PROTOCOLLNPGM(MSG_FILE_SAVED);
 
-          #ifndef USBCON
+          #if !(defined(__AVR__) && defined(USBCON))
             #if ENABLED(SERIAL_STATS_DROPPED_RX)
               SERIAL_ECHOLNPAIR("Dropped bytes: ", customizedSerial.dropped());
             #endif
@@ -13856,7 +13856,7 @@ void loop() {
             #if ENABLED(SERIAL_STATS_MAX_RX_QUEUED)
               SERIAL_ECHOLNPAIR("Max RX Queue Size: ", customizedSerial.rxMaxEnqueued());
             #endif
-          #endif // !USBCON
+          #endif // !(__AVR__ && USBCON)
 
           ok_to_send();
         }
diff --git a/Marlin/SanityCheck.h b/Marlin/SanityCheck.h
index 77d7fa0e6..15e49ddf9 100644
--- a/Marlin/SanityCheck.h
+++ b/Marlin/SanityCheck.h
@@ -275,7 +275,7 @@
 /**
  * Serial
  */
-#ifndef USBCON
+#if !(defined(__AVR__) && defined(USBCON))
   #if ENABLED(SERIAL_XON_XOFF) && RX_BUFFER_SIZE < 1024
     #error "SERIAL_XON_XOFF requires RX_BUFFER_SIZE >= 1024 for reliable transfers without drops."
   #elif RX_BUFFER_SIZE && (RX_BUFFER_SIZE < 2 || !IS_POWER_OF_2(RX_BUFFER_SIZE))
@@ -1281,7 +1281,7 @@ static_assert(1 >= 0
 /**
  * emergency-command parser
  */
-#if ENABLED(EMERGENCY_PARSER) && defined(USBCON)
+#if ENABLED(EMERGENCY_PARSER) && defined(__AVR__) && defined(USBCON)
   #error "EMERGENCY_PARSER does not work on boards with AT90USB processors (USBCON)."
 #endif
 
diff --git a/Marlin/serial.h b/Marlin/serial.h
index 994657121..dc1da8735 100644
--- a/Marlin/serial.h
+++ b/Marlin/serial.h
@@ -25,7 +25,7 @@
 
 #include "MarlinConfig.h"
 
-#ifdef USBCON
+#if defined(__AVR__) && defined(USBCON)
   #include <HardwareSerial.h>
   #if ENABLED(BLUETOOTH)
     extern HardwareSerial bluetoothSerial;