The Queen of Wimbledon, played her first match back at Wimbledon since winning her seventh title in 2016 and overcame rustiness and blustering conditions to win 7-5 6-3.
Serena Williams, playing only her ninth match since returning from giving birth to her first child, did not have things all her own way as her Dutch opponent threatened to cause a surprise result.
The world No 181 made an encouraging start in front of the Court 1 crowd to break Rus at the first opportunity but her early advantage was quickly pegged back by her inspired opponent in the first meeting between the pair.
Both players held serve until the 12th game of the opener before Williams secured a decisive break to clinch the first set and take the initiative.
Despite the setback of losing the first, Rus continued to compete well at the start of the second and broke Williams in the third game before an assured hold moved her 3-1 ahead.
Williams upped her level of performance to win five straight games, closing out victory with her sixth match point to book a meeting with Tereza Smitkova or Viktoriya Tomova next.