diff --git a/Marlin/Configuration.h b/Marlin/Configuration.h
index 462bfff65b4d..37df8c0c57d5 100644
--- a/Marlin/Configuration.h
+++ b/Marlin/Configuration.h
@@ -3305,6 +3305,7 @@
     #define NEOPIXEL2_PIXELS           15 // Number of LEDs in the second strip
     #define NEOPIXEL2_BRIGHTNESS      127 // Initial brightness (0-255)
     #define NEOPIXEL2_STARTUP_TEST        // Cycle through colors at startup
+    #define NEOPIXEL_M150_DEFAULT      -1 // Default strip for M150 without 'S'. Use -1 to set all by default.
   #else
     //#define NEOPIXEL2_INSERIES          // Default behavior is NeoPixel 2 in parallel
   #endif
diff --git a/Marlin/src/gcode/feature/leds/M150.cpp b/Marlin/src/gcode/feature/leds/M150.cpp
index 77c58411a37a..43062c3f752a 100644
--- a/Marlin/src/gcode/feature/leds/M150.cpp
+++ b/Marlin/src/gcode/feature/leds/M150.cpp
@@ -61,7 +61,12 @@ void GcodeSuite::M150() {
   #if ENABLED(NEOPIXEL_LED)
     const pixel_index_t index = parser.intval('I', -1);
     #if ENABLED(NEOPIXEL2_SEPARATE)
-      int8_t brightness = neo.brightness(), unit = parser.intval('S', -1);
+      #ifndef NEOPIXEL_M150_DEFAULT
+        #define NEOPIXEL_M150_DEFAULT -1
+      #elif NEOPIXEL_M150_DEFAULT > 1
+        #error "NEOPIXEL_M150_DEFAULT must be -1, 0, or 1."
+      #endif
+      int8_t brightness = neo.brightness(), unit = parser.intval('S', NEOPIXEL_M150_DEFAULT);
       switch (unit) {
         case -1: neo2.neoindex = index; // fall-thru
         case  0:  neo.neoindex = index; old_color = parser.seen('K') ? neo.pixel_color(index >= 0 ? index : 0) : 0; break;