Bo Jackson has the most rushing yards in a game on Mondays, with 221 yards against the Seahawks on November 30, 1987.

most monday night football rushing yards, single game
Interpreted as:
most monday night football rushing yards by a player, single regular-season game
11/30/1987Jackson12/9/2002Williams9/24/1990Thomas11/17/2014Bell11/27/2006Alexander11/20/1978Campbell12/6/2004Jones12/14/1998Hearst11/17/1975Simpson9/19/1994Sanders11/10/2003Green12/8/2008Williams9/9/2013McCoy11/24/2014Forsett10/27/1986Morris11/26/2012Brown11/29/2004Davenport9/29/2003Green12/10/1990Sanders12/23/1996Sanders12/21/1992Smith10/14/1985McNeil12/6/1993Smith221216214204201199198198197194192186184182181178178176176175174173172
NAMEDATETMOPPRUSH YDSATTYPCRUSH TDREC YDSRECTRGAVGREC TD
Bo JacksonBo Jackson11/30/1987RAIRAI@SEASEA2211812.3214114.01
Ricky WilliamsRicky Williams12/9/2002MIAMIAvsCHICHI216317.020030
Thurman ThomasThurman Thomas9/24/1990BUFBUF@NYJNYJ2141811.90531.70
Le'Veon BellLe'Veon Bell11/17/2014PITPIT@TENTEN204336.2118249.00
Shaun AlexanderShaun Alexander11/27/2006SEASEAvsGBGB201405.000010
Earl CampbellEarl Campbell11/20/1978HOUHOUvsMIAMIA199287.14000
Julius JonesJulius Jones12/6/2004DALDAL@SEASEA198306.6311373.70
Garrison HearstGarrison Hearst12/14/1998SFSFvsDETDET198248.31000
O.J. SimpsonO.J. Simpson11/17/1975BUFBUF@CINCIN1971711.6221210.50
Barry SandersBarry Sanders9/19/1994DETDET@DALDAL194404.90000
Ahman GreenAhman Green11/10/2003GBGBvsPHIPHI192296.61323410.71
DeAngelo WilliamsDeAngelo Williams12/8/2008CARCARvsTBTB186199.826116.00
LeSean McCoyLeSean McCoy9/9/2013PHIPHI@WASWAS184315.915115.00
Justin ForsettJustin Forsett11/24/2014BALBAL@NONO182228.328224.00
Joe MorrisJoe Morris10/27/1986NYGNYGvsWASWAS181315.8259511.80
Bryce BrownBryce Brown11/26/2012PHIPHIvsCARCAR178199.4211452.80
Najeh DavenportNajeh Davenport11/29/2004GBGBvsSTLSTL178199.418118.00
Ahman GreenAhman Green9/29/2003GBGB@CHICHI176199.324441.00
Barry SandersBarry Sanders12/10/1990DETDETvsRAIRAI176257.021635.30
Barry SandersBarry Sanders12/23/1996DETDET@SFSF175286.31414.00
Emmitt SmithEmmitt Smith12/21/1992DALDAL@ATLATL174247.32522.50
Freeman McNeilFreeman McNeil10/14/1985NYJNYJvsMIAMIA173286.2046315.30
Emmitt SmithEmmitt Smith12/6/1993DALDALvsPHIPHI172237.502646.50
Terrell DavisTerrell Davis10/6/1997DENDENvsNENE171325.32723.50
Carlos HydeCarlos Hyde9/14/2015SFSFvsMINMIN168266.5214227.00
Results may be incomplete. StatMuse has complete game-level data for rushing yards going back to the 1960 season.