• Diagnosis of CLL or SLL according to WHO criteria

• Participants must require therapy according to iwCLL 2018 guidelines

• Participants must have ≥ 2 points (high or intermediate risk disease) according to the CLL

∙ BALL Risk Model:

• Beta-2 microglobulin If ≥ 5 mg/L, assign 1 point

• Lactate dehydrogenase If \>institutional upper limit of normal, assign 1 point

• Hemoglobin If \<11 g/dL (female) or \<12 g/dL (male), assign 1 point

• Time from start of last therapy If \<24 months, assign 1 point, If 4 points, patient is high risk, If 2-3 points, patient is intermediate risk, If 0-1 points, patient is low risk

‣ Participants must have received prior systemic therapy for CLL

⁃ Age over 18 years

⁃ ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)

⁃ Participants must have adequate organ function as defined below:

• total bilirubin ≤2 × institutional upper limit of normal unless considered secondary to Gilbert's syndrome, in which case ≤3 x ULN

• AST(SGOT)/ALT(SGPT) ≤2 × institutional upper limit of normal

• creatinine within normal institutional limits OR

• creatinine clearance ≥30 mL/min according to the Cockcroft-Gault Equation for participants with creatinine levels above institutional normal.

‣ Participants must have adequate marrow function as defined below (unless clearly due to disease under study per investigator discretion)

• absolute neutrophil count ≥1,000/mcL

• platelets ≥75,000/mcL OR

• \> 20,000/mcL if thrombocytopenia is clearly due to disease under study (per investigator discretion).

‣ For females of childbearing potential, a negative serum pregnancy test within 7 days of study treatment

⁃ For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use highly effective form(s) of contraception (i.e., one that results in a low failure rate \[\<1% per year\] when used consistently and correctly) and to continue its use for 90 days after the last dose of acalabrutinib or venetoclax AND for 18 months after the last dose of obinutuzumab (whichever date is later)

⁃ The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.

⁃ Willingness to not donate sperm or oocytes during the entire study treatment period and after treatment discontinuation

⁃ Ability to understand and the willingness to sign a written informed consent document.