The Liverpool superstar scored twice in a 3-0 victory over Djibouti on Wednesday to ensure Egypt will top its African qualifying group with one round to spare.
Egypt is the third African team to qualify so far — joining Morocco and Tunisia. Ibrahim Adel also scored for Egypt.
Salah and Egypt went to the 2018 World Cup, but he was affected by a shoulder injury sustained in the Champions League final weeks earlier, when Liverpool lost to Real Madrid.
At that edition, Egypt lost all three of its group games — against host Russia, Uruguay and Saudi Arabia.
Egypt will be among nine African teams that directly qualify in the World Cup tournament draw on Dec. 5 in Washington D.C.
Burkina Faso second behind Egypt in Group A after its 1-0 win at Sierra Leone, while Ethiopia beat Guinea Bissau 1-0.
Cape Verde fought back from 3-1 down to draw 3-3 against Libya to edge closer to what would be its first-ever World Cup qualification.
Cape Verde leads Group D by two points over Cameroon, which beat Mauritius 2-0 — Nicolas Ngamaleu and Bryan Mbeumo both scored.
