Diana Taurasi, Breanna Stewart and Sylvia Fowles each netted 15 points to lead seven double-figure scorers for the Americans, all of whom produced points to set a one-game US Olympic record in the Group B preliminary round match.
The 65-point victory margin surpassed the prior US mark from a 107-47 victory over the Democratic Republic of Congo set at the 1996 Atlanta Olympics.
"Records at the end of the day are fun to look back on, but more than anything regardless of the score it's beautiful basketball," US co-captain Sue Bird said.
"Nobody cares who gets the points. Lucky for us we have a lot of scorers. No matter who is in the game (they) can put a lot of big numbers."
Brittney Griner added 14 points and matched Fowles with a game-high seven rebounds in her US Olympic debut. Fellow newcomer Elena Delle Donne had 11 points and six assists.
Fatou Dieng scored 10 points to lead Senegal, the 2015 African champions.
The US women have made unbeaten runs to titles in seven of the past eight Olympic tournaments and four of the past five World Championships as well. 
Next up for the Americans is Spain, whose best Olympic finish was fourth in 2008. The Spaniards opened by beating Serbia 65-59 as Marta Xargay had 15 points, Anna Cruz added 13 points and 11 rebounds and Astou Ndour contributed 11 points and 12 rebounds.
In Group A, Australia outlasted Turkey 61-56 with Elizabeth Cambage scoring 22 points and grabbing 11 rebounds for the 2-0 Opals. Lara Sanders had 25 points in a losing cause.