In their second match in four days, Mexico looked sharper than they did in Friday's goalless draw against Ecuador at Giants Stadium. Medina and Cuauhtemoc Blanco came on in the 56th and immediately energized Mexico.
On the hour mark Andres Guardado, who replaced Israel Castro at half-time, fired a long pass ahead of Medina. Senegal keeper Khadim Ndiaye came out to collect the ball but slid too far and let it get away. That left the charging Medina free to bury the ball in the net.
The goal drew a wild ovation from the sell-out crowd of 60,610 at Soldier Field. But Mexico couldn't capitalize on efforts from Blanco and Javier Hernandez - who is due to join Manchester United in July.
Minutes after Medina scored Hernandez let a chance to double the score get away as he didn't get to a ball from Paul Aguilar. Blanco had a point-blank opportunity in the final minute but sent his shot straight at Ndiaye.
They play friendlies in Europe against England, the Netherlands and Italy before opening the 2010 FIFA World Cup against hosts South Africa on 11 June. Mexico's first-round group also includes France and Uruguay.