Over the past decade, force-velocity (F-v) profiling has emerged as a promising tool for assessing neuromuscular capacity to design individually tailored interventions in diverse populations. To date, a limited number of studies have addressed the optimization of the linear method for measuring F-v profiles of single-joint isokinetic movements. We aimed to simplify the measurement of knee extension (KE) and knee flexion (KF) isokinetic tasks by evaluating the most appropriate combination of two velocities (i.e., the 2-point method). Twenty-two healthy participants (11 males and 11 females) were included in the study. Isokinetic peak torque was measured at nine angular velocities (30-60-90-120-150-180-210-240-300°/s) and under isometric conditions (at 150° and 120° of KF for KE, and KF, respectively). Maximal theoretical force (F0), maximal theoretical velocity (v0), slope of the relationship (Sfv) and maximal theoretical power (Pmax) were derived from the linear F-v profiles of KE and KF and compared between the 9-point method and all possible combinations (36 in total) of the 2-point methods. The F-v profiles obtained from nine points were linear for KE (R2 = 0.95; 95% CI = 0.94–0.96) and KF (R2 = 0.93; 95% CI = 0.90–0.95), with F0 underestimating isometric force. Further analyses revealed great to excellent validity (range: ICCs = 0.89–0.99; CV = 2.54%–4.34%) and trivial systematic error (range: ES = −0.11–0.24) of the KE 2-point method when force from distant velocities (30°/s, 60°/s or 90°/s combined with 210°/s, 240°/s or 300°/s) was used. Similarly, great to excellent validity and trivial systematic error of the KF 2-point method for F0 and Pmax (range: ICC = 0.90–0.96; CV = 2.94%–6.38%; ES = −0.07–0.14) were observed when using the previously described combinations of velocities. These results suggest that practitioners should consider using more distant velocities when performing simplified isokinetic 2-point single-joint F-v profiling. Furthermore, the F-v profile has the potential to differentiate between the mechanical properties of knee extensors and flexors and could therefore serve as a potential descriptor of performance.