Defoe, 34, was making his first England appearance since November 2013, having been recalled by manager Gareth Southgate, and he marked his return with the opening goal midway through the second half.
Substitute Jamie Vardy added a second goal as England tightened its grip on first place in UEFA qualifying Group F in Southgate's first home game as permanent manager.
His side is now the last team in European qualifying yet to have conceded a goal.
But the stubbornly unadventurous nature of Lithuania's approach to the game, which made for a soporific match, meant there was little to shout about from an England perspective.
The game was preceded by the laying of wreaths and a minute's silence in honour of the four people killed and over 50 injured in Wednesday's terror attack in London.
Having tested out a 3-4-2-1 system in the mid-week 1-0 friendly defeat in Germany, Southgate reverted to a back four and his side was quickly on the front foot, with Adam Lallana prominent.
Defoe's penalty-box cunning was one of the reasons Southgate picked him over Vardy, and he vindicated his manager's call by putting England ahead in the 22nd minute.