Background Postpartum depression (PPD) and postpartum anxiety (PPA) are often comorbid and are associated with significant personal and economic costs. Fewer than half of the mothers experiencing PPD or PPA symptoms receive face-to-face treatment, suggesting a need for alternative delivery formats such as internet-delivered cognitive behavioral therapy (ICBT). Objective This pilot study aimed to examine the impact of a therapist-assisted, transdiagnostic ICBT program on symptoms of PPD and PPA, as there is only one previous study on transdiagnostic ICBT with this population, which did not include therapist assistance. Methods Clients endorsing the symptoms of PPD or PPA (N=63) were randomized to an 8-week transdiagnostic ICBT course (Wellbeing Course for New Moms) or to treatment as usual (TAU). Clients completed measures of depression, anxiety, stress, postnatal bonding, and relationship satisfaction, as well as measures of treatment satisfaction and therapeutic alliance, before treatment, after treatment, and at the 1-month follow-up. Outcome measures were also completed at the 6-month follow-up for clients who completed the ICBT course. Results Both the ICBT and TAU groups experienced statistically significant improvements over time. The ICBT group experienced larger improvements after treatment and at the 1-month follow-up on more measures than the TAU group, with medium between-group Cohen d effects on primary outcome measures for anxiety (Cohen d=0.65, 95% CI 0.13-1.17), PPD (Cohen d=0.52, 95% CI 0.01-1.04), and depression (Cohen d=0.56, 95% CI 0.05-1.08), and on secondary outcome measures of overall distress (Cohen d=0.69, 95% CI 0.17-1.21), anxiety (Cohen d=0.59, 95% CI 0.07-1.11), and stress (Cohen d=0.76, 95% CI 0.23-1.28). Time-by-group interactions for proportional reductions between groups over time were only significant after treatment and at the 1-month follow-up for the primary anxiety measure (P=.006). This study was underpowered for detecting small or medium effects. Overall, clients perceived the treatment as credible, and 95% (21/22) of the clients were satisfied with the treatment content and therapist support. Conclusions Findings from this pilot study provide preliminary support for transdiagnostic ICBT in treating PPD and PPA symptoms to improve access to psychological treatments. Trial Registration ClinicalTrials.gov NCT04012580; https://clinicaltrials.gov/ct2/show/NCT04012580