As the leader of the Uganda National Liberation Front (UNLF), Lule was installed as President by neighbouring Tanzania who had toppled Idi Amin with help from the UNLF after his failed attempt to annex portions of Tanzania (see Uganda-Tanzania War). Lule was the first of a swift succession of Ugandan leaders before the eventual return of Milton Obote in 1980.
Lule's government adopted a ministerial system of administration and created a quasi-parliamentary organ known as the National Consultative Commission (NCC). The NCC and the Lule cabinet reflected widely differing political views. In June 1979, following a dispute over the extent of presidential powers, the NCC replaced Lule with Godfrey Binaisa.
Out of office, he led the Uganda Freedom Fighters (UFF), a resistance group which joined with Yoweri Museveni's Popular Resistance Army (PRA) in 1981. The combined National Resistance Army (NRA) eventually succeeded in overthrowing Tito Lutwa Okello and taking power in 1986.
Lule, however, had already died in 1985 of kidney failure.