Blackmon ran awkwardly to first base while beating out an infield single in the top of the first inning. The four-time All-Star stayed in the game for the remainder of the opening frame before being replaced by Wynton Bernard before the bottom of the second.
Senzatela suffered a left knee injury in the bottom of the second while attempting to cover first base on a grounder by St. Louis' Brendan Donovan.
The veteran right-hander fell to the ground near first base and eventually was helped to the Rockies' dugout after a lengthy evaluation.
Rockies manager Bud Black said Blackmon is not expected to go on the injured list, but will probably not start in the next game. He wasn't as confident on Senzatela's outlook.
Both players will be reevaluated tomorrow.
"Antonio is going to get a MRI in the morning,'' Black said. "He definitely has a (left) knee sprain to a certain extent. How significant? We won't know until tomorrow. Devastating, right?''
Blackmon, 36, is batting .264 with 16 home runs and 67 RBIs this season, his 12th with the Rockies. Senzatela, who was replaced by left-hander Austin Gomber, is 3-6 with a 5.07 ERA in 19 starts this season.