Suspicion of failure in the effectiveness of artemisinin-based combination therapies (currently the first-line treatment of malaria, worldwide) is leading to the unofficial use of alternative antimalarials, including chloroquine and sulfadoxine/pyrimethamine, across northern Nigeria. To facilitate evidence-based resistance management, antimalarial resistance mutations were investigated in Plasmodium falciparum multidrug resistance-1 (pfmdr1) and chloroquine resistance transporter (pfcrt), in isolates from Kano, northwestern Nigeria. Out of the 88 samples genotyped for pfmdr1 N86Y mutation using PCR/restriction fragment length polymorphism, one sample contained the 86Y mutation (86Y_frequency = 1.14%). The analysis of 610 bp fragments of pfmdr1 from 16 isolates revealed two polymorphic sites and low haplotype diversity (H_d = 0.492), with only 86 Y mutations in one isolate, and 184 F replacements in five isolates (184F_frequency = 31.25%). The analysis of 267 bp fragments of pfcrt isolates revealed high polymorphism (H_d = 0.719), with six haplotypes and seven non-synonymous polymorphic sites. Eleven isolates (61.11%) were chloroquine-resistant, CQR (C₇₂V₇₃I₇₄E₇₅T₇₆ haplotype), two of which had an additional mutation, D⁵⁷E. An additional sequence was CQR, but of the C₇₂V₇₃M₇₄E₇₅T₇₆ haplotype, while the rest of the sequences (33.33%) were chloroquine susceptible (C₇₂V₇₃M₇₄N₇₅K₇₆ haplotype). The findings of these well characterized resistance markers should be considered when designing resistance management strategies in the northwestern Nigeria.