The 34-year-old was last named in a starting line-up for his country on March 22, 2013, when he scored two goals on the way to an 8-0 win over San Marino.
Defoe lines up at Wembley for the first time since September 11, 2012, when England drew 1-1 with Ukraine, and gets the nod on Sunday ahead of Jamie Vardy and Marcus Rashford.
Joe Hart has been named as captain, with Wayne Rooney not called up and Gary Cahill suspended. Cahill's absence has seen Gareth Southgate revert back to a four-man defence.
Uncapped Ben Gibson was called up as a replacement for Chris Smalling, who withdraw on Friday with injury, but starts his senior career on the bench.
England XI: Hart, Walker, Keane, Stones, Bertrand, Dier, Oxlade-Chamberlain, Sterling, Lallana, Alli, Defoe
Lithuania XI: Setkus, Vaitkunas, Kijanskas, Klimavicius, Slavickas, Kuklys, Zulpa, Novikovas, Slivka, Cernych, Valskis
WHAT THEY SAID
Gareth Southgate: "We know how important the national football team is for the feeling of the nation, and it's a great opportunity for everybody to pay their respects at that moment, and to show we go on," said Southgate.
"Not just London, but the nation. That's our identity, historically. I thought the tribute before the France game was very poignant. This will be the same."
Edgaras Jankauskas: "First of all it's a privilege to play at such a legendary stadium and probably one of the best stadiums in the world.
"There are always chances and chances depend on us, (there are) many examples where not necessarily the favourites win the game. We are a humble team but we have our game plan and we'll stick to that.