Adenine base editors (ABE) are novel genome-editing tools that have been harnessed to introduce precise A•T to G•C conversion in genomic DNA. However, the low activity of ABE remains a major bottleneck that precludes efficacious applications. To address this limitation, we developed a directional screening system in human cells to evolve the deaminase component of the ABE, and identified three high-activity NG-ABEmax variants: NG-ABEmax-SGK (R101S/D139G/E140K), NG-ABEmax-R (Q154R) and NG-ABEmax-K (N127K). With further engineering, we created a new, consolidated variant [NG-ABEmax-KR (N127K/Q154R)] which exhibited superior editing activity both in human cells and in mouse disease models, compared to the original NG-ABEmax. We also found that NG-ABEmax-KR efficiently introduce natural mutations in gamma globin gene promoters with more than four-fold increase in editing activity. This work provides a broadly applicable, rapidly deployable platform to directionally screen and evolve novel, user-specified traits in base editors that extend beyond augmented editing activity.